Dissolution testing is required for all solid oral pharmaceutical solid dosage form forms in which absorption of the drug is necessary for the product to exert the desired therapeutic effect. The U.S. Pharmacopeia (USP) is one well-known standard source of information which provides for dissolution and drug release testing in the majority of monographs for such dosage forms. Exceptions are for tablets meeting a requirement for completeness of solution or for rapid (10 to 15 minutes) disintegration for soluble or radiolabled drugs. The apparatus and procedure conform to the requirements and specificaitons given, e.g., USP 23rd edition Chapter 711 (Dissolution) pages 1791-1793. Dissolution testing serves as a measure of quality control, stability and uniformity as well as a means by which to correlate in-vitro with in-vivo drug release characteristics.
Current USP dissolution methods most commonly employ a temperature programmable water bath, maintained at about 37.degree. C., in which sample vessels are submerged. These vessels contain a predetermined volume of a dissolution media and a means to agitate the contents of the vessel. This may be accomplished by means of a rotating basket attached to a shaft or with a paddle which is also attached to a shaft, both means generally described in USP 23rd edition Chapter 711 (Dissolution) pages 1791-1793. The solid dosage form is placed into the media filled vessel at time zero and specific vessel temperature and mixing speeds are maintained. At fixed time intervals (e.g. 2, 4, 8 hours, etc.) a small aliquot of sample is taken from each vessel, usually by a multi channeled pumping system, and transported to either a cuvette or a sample vial for subsequent spectrophotometric or high pressure liquid chromatography (HPLC) analysis, respectively. Plotting percentage dissolution of a solid dosage form through time results in a dissolution profile.
Of the two methods discussed above, the HPLC method is usually favored over the spectrophotometric method. While HPLC dissolution offers the advantage of specificity, acceptable accuracy, precision and sensitivity, the disadvantage of the status quo rather lies with the inherent burden of creating, manipulating, and storing voluminous numbers of sequence and data files. The cost of TPLC, columns, mobile phases, and the waste solvent disposal, etc., is substantial and the limited number of data points that can be determined may result in a less than ideal representation of the release profile of a solid dosage form over time. Furthermore, HPLC analysis is a sequential time consuming process. In general, a typical 24 hour dissolution requires up to 60 hours to generate a dissolution profile.
Because of the aforementioned disadvantages of currently available systems, an in-situ dissolution method is desirable.